title: Randomized multicenter phase II trial comparing two schedules of etirinotecan pegol (NKTR-102) in women with recurrent platinum-resistant/refractory epithelial ovarian cancer.
abstract: OBJECTIVE
  Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma.
  
  
  METHODS
  A total of 71 eligible patients were randomly assigned to receive etirinotecan pegol 145 mg/m(2) every 14 or 21 days until progression or unacceptable adverse events (AEs). The primary end point was objective response rate (ORR) by RECIST (version 1.0). Secondary end points included response by Gynecologic Cancer Intergroup criteria, duration of ORR, progression-free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  The overall confirmed ORR was 20% (95% CI, 10% to 30%): 20% for once every 14 days, and 19% for once every 21 days. Median response duration was 4.1 months for once every 14 days and 4.0 months for once every 21 days. Median PFS for every 14 and every 21 days was 4.1 and 5.3 months, respectively, and median OS was 10.0 and 11.7 months, respectively. Etirinotecan pegol was well tolerated, with the most common grade 3 to 4 AEs being dehydration (24%) and diarrhea (23%). Diarrhea, dehydration, nausea, and neutropenia were less frequent with the schedule of once every 21 days than with that of once every 14 days.
  
  
  CONCLUSIONS
  Both schedules of etirinotecan pegol showed activity in patients with heavily pretreated ovarian cancer, with encouraging ORR and PFS rates. The schedule of once every 21 days was better tolerated and had slightly longer PFS and OS rates. The treatment schedule of etirinotecan pegol 145 mg/m(2) once every 21 days was selected for the expanded phase II study and is preferred for future phase III studies. These findings provide support to directly compare etirinotecan pegol versus one of the approved drugs (eg, pegylated liposomal doxorubicin or topotecan) in platinum-resistant ovarian cancer.
authors.affiliation: Ignace B. Vergote, University Hospital Leuven, Leuven; Christine Gennigens, Centre Hospitalier Universitaire de Liège, Liège; Luc Y. Dirix, Gasthuis Zusters Antwerpen, Antwerp, Belgium; Agustin Garcia, University of Southern California Norris Comprehensive Cancer Center and Hospital, Los Angeles; John Micha, Gynecologic Oncology Associates, Newport Beach; Emad N. Ibrahim, Beaver Medical Group, Redlands; Abraham C.F. Leung, Carol Zhao, and Raoudha Soufi-Mahjoubi, Nektar Therapeutics, San Francisco, CA; Charles Pippitt, Piedmont Hematology Oncology Associates, Winston Salem, NC; Johanna Bendell, Sarah Cannon Research Institute, Nashville, TN; Daniel Spitz, Palm Beach Cancer Institute, West Palm Beach, FL; Nicholas Reed, Beatson Oncology Centre, Glasgow; Graham Dark, Freeman Hospital, Newcastle upon Tyne; Chris Poole, University Hospital Coventry, Coventry; Gordon Rustin, Mount Vernon Hospital, Northwood, United Kingdom; Paula M. Fracasso and Linda Duska, University of Virginia Health System, Charlottesville, VA; and Vincent A. Armenio, Pharma Resource, Providence, RI.
authors.forename: Ignace B
authors.initials: IB
authors.lastname: Vergote
authors.forename: Agustin
authors.initials: A
authors.lastname: Garcia
authors.forename: John
authors.initials: J
authors.lastname: Micha
authors.forename: Charles
authors.initials: C
authors.lastname: Pippitt
authors.forename: Johanna
authors.initials: J
authors.lastname: Bendell
authors.forename: Daniel
authors.initials: D
authors.lastname: Spitz
authors.forename: Nicholas
authors.initials: N
authors.lastname: Reed
authors.forename: Graham
authors.initials: G
authors.lastname: Dark
authors.forename: Paula M
authors.initials: PM
authors.lastname: Fracasso
authors.forename: Emad N
authors.initials: EN
authors.lastname: Ibrahim
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Armenio
authors.forename: Linda
authors.initials: L
authors.lastname: Duska
authors.forename: Chris
authors.initials: C
authors.lastname: Poole
authors.forename: Christine
authors.initials: C
authors.lastname: Gennigens
authors.forename: Luc Y
authors.initials: LY
authors.lastname: Dirix
authors.forename: Abraham C F
authors.initials: AC
authors.lastname: Leung
authors.forename: Carol
authors.initials: C
authors.lastname: Zhao
authors.forename: Raoudha
authors.initials: R
authors.lastname: Soufi-Mahjoubi
authors.forename: Gordon
authors.initials: G
authors.lastname: Rustin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017671:Platinum Compounds / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; D017671:Platinum Compounds; D011092:Polyethylene Glycols; C581703:etirinotecan pegol